Glucose-dependent insulinotropic polypeptide receptor knockout mice are impaired in learning, synaptic plasticity, and neurogenesis.

Glucose-dependent insulinotropic polypeptide (GIP) is a key incretin hormone, released from intestine after a meal, producing a glucose-dependent insulin secretion. The GIP receptor (GIPR) is expressed on pyramidal neurons in the cortex and hippocampus, and GIP is synthesized in a subset of neurons in the brain. However, the role of the GIPR in neuronal signaling is not clear. In this study, we used a mouse strain with GIPR gene deletion (GIPR KO) to elucidate the role of the GIPR in neuronal communication and brain function. Compared with C57BL/6 control mice, GIPR KO mice displayed higher locomotor activity in an open-field task. Impairment of recognition and spatial learning and memory of GIPR KO mice were found in the object recognition task and a spatial water maze task, respectively. In an object location task, no impairment was found. GIPR KO mice also showed impaired synaptic plasticity in paired-pulse facilitation and a block of long-term potentiation in area CA1 of the hippocampus. Moreover, a large decrease in the number of neuronal progenitor cells was found in the dentate gyrus of transgenic mice, although the numbers of young neurons was not changed. Together the results suggest that GIP receptors play an important role in cognition, neurotransmission, and cell proliferation.

Role of glutathione deficit in the disconnectivity syndrome in schizophrenia: from pathogenetic mechanisms to therapeutic interventions

In the cerebrospinal fluid of 26 drug-naive schizophrenics (DSM-III- R), we observed that the level of glutathione ([GSH]) and of its metabolite γ-Glu-Gln was decreased by 27% and 16% respectively. Using a new in-vivo method based on magnetic resonance spec- troscopy, [GSH] was measured in the medial prefrontal cortex of 18 schizophrenics and found to be 52 % lower than in controls (n = 20). This is consistent with the recently observed decreased mRNA levels in fibroblasts of patients (n=32) of the two GSH synthesizing en- zymes (glutathione synthetase (GSS), and glutamate-cysteine ligase M (GCLM) the modulatory subunit of glutamate-cysteine ligase). Moreover, the level of GCLM expression in fibroblasts correlates neg- atively with the psychopathology (positive, general and some nega- tive symptoms). Thus, the observed difference in gene expression is not only the cause of low brain [GSH], but is also related to the sever- ity of symptoms, suggesting that fibroblasts are adequate surrogate for brain tissue. A hypothesis was proposed, based on a central role of GSH in the pathophysiology of schizophrenia. GSH is an important endogenous redox regulator and neuroactive substance. GSH is pro- tecting cells from damage by reactive oxygen species generated, among others, by the metabolism of dopamine. A GSH deficit-in- duced oxidative stress would lead to lipid peroxidation and micro-le- sions in the surrounding of catecholamine terminals, affecting the synaptic contacts on dendritic spines of cortical neurones, where ex- citatory glutamatergic terminals converge with dopaminergic ones. This would lead to spines degeneration and abnormal nervous con- nections or structural disconnectivity, possibly responsible for posi- tive, perceptive and cognitive symptoms of schizophrenia. In addi- tion, a GSH deficit could also lead to a functional disconnectivity by depressing NMDA neurotransmission, in analogy to phencyclidine effects. Present experimental biochemical, cell biological and behav- ioral data are consistent with the proposed mechanism: decreasing pharmacologically [GSH] in experimental models, with or without blocking DA uptake (GBR12909), induces morphological and behav- ioral changes similar to those observed in patients. Dendritic spines: (a) In neuronal cultures, low [GSH] and DA induce decreased density of neural processes; (b) In developing rats (p5-p16), [GSH] deficit and GBR induce a decrease in normal spines in prefrontal pyramids and in GABA-parvalbumine but not of -calretinine immunoreactivity in anterior cingulate. NMDA-dependant synaptic plasticity: GSH deple- I/13 tion in hippocampal slices impairs long-term potentiation. Develop- ing rats with low [GSH] and GBR have deficit in olfactory integration and in object recognition which appears earlier in males than fe- males, in analogy to the delay of the psychosis onset between man and woman. In summary, a deficit of GSH and/or GSH-related enzymes during early development could constitute a major vulnerability fac- tor in schizophrenia.

Human epidermal cultures screened for residual murine feeder cells-No contaminants found

Rationale: Human keratinocytes used for transplants are cultivated on a feeder layer which may be composed of autologous human fibroblasts or 3T3 murine fibroblasts. Using the latter method spares 15 additional days of preparation. In this study we investigate the potential presence of residual murine feeder cell contaminants in epidermal cultures prepared for transplantation. Methods: Monolayers of cultured 3T3-J2 murine fibroblasts were treated with 4 μg/mL of mitomycin C (MMC) for 2 h and used to track cell survival kinetics. Using similar 3T3 cells, human keratinocyte cultures were grown following a modified protocol based on the method described by Rheinwald and Green. Cell sheets were mechanically detached and rinsed 4 times following the same procedure used for transplant preparation. The elimination of 3T3 cells during culture was visually tracked using phase contrast microscopy. Epidermal cultures were then dissociated to produce cell suspensions and analyzed by flow cytometry using a murine-specific antibody, CD90, conjugated to a fluorescein isothiocyanate (FITC) marker. Dead cells were identified using 7-amino-actinomysin D (7-AAD) which binds to DNA in permeabilized cells. Results: 3T3 cells treated with MMC display clear morphological signs of apoptosis, disappearing completely in 9-10 days following kinetics similar to 30 Gy gamma irradiated 3T3 cells. Histological analysis of cultured epidermal sheets revealed homogenous keratinocytic tissue with no 3T3 cells. MMC treated and untreated 3T3 cells displayed strong CD90 expression. Cell suspensions obtained from epidermal cultures were, however, negative for that marker. Conclusion: Results obtained demonstrate the absence of contaminating murine 3T3 feeder cells in human keratinocyte cultures. These findings highlight our success in developing cultured human epidermal autografts.

Development of Object-Oriented Design and Specifications for Iowa DOT and Urban Standards: Phase I, TR-487, 2004

Currently, individuals including designers, contractors, and owners learn about the project requirements by studying a combination of paper and electronic copies of the construction documents including the drawings, specifications (standard and supplemental), road and bridge standard drawings, design criteria, contracts, addenda, and change orders. This can be a tedious process since one needs to go back and forth between the various documents (paper or electronic) to obtain information about the entire project. Object-oriented computer-aided design (OO-CAD) is an innovative technology that can bring a change to this process by graphical portrayal of information. OO-CAD allows users to point and click on portions of an object-oriented drawing that are then linked to relevant databases of information (e.g., specifications, procurement status, and shop drawings). The vision of this study is to turn paper-based design standards and construction specifications into an object-oriented design and specification (OODAS) system or a visual electronic reference library (ERL). Individuals can use the system through a handheld wireless book-size laptop that includes all of the necessary software for operating in a 3D environment. All parties involved in transportation projects can access all of the standards and requirements simultaneously using a 3D graphical interface. By using this system, users will have all of the design elements and all of the specifications readily available without concerns of omissions. A prototype object-oriented model was created and demonstrated to potential users representing counties, cities, and the state. Findings suggest that a system like this could improve productivity to find information by as much as 75% and provide a greater sense of confidence that all relevant information had been identified. It was also apparent that this system would be used by more people in construction than in design. There was also concern related to the cost to develop and maintain the complete system. The future direction should focus on a project-based system that can help the contractors and DOT inspectors find information (e.g., road standards, specifications, instructional memorandums) more rapidly as it pertains to a specific project.

Bridge Rail and Approach Railing for Low-Volume Roads in Iowa, TR-592, 2010

Bridge rail and approach guardrails provide safety to drivers by shielding more hazardous objects and redirecting vehicles to the roadway. However, guardrail can increase both the initial cost and maintenance cost of a bridge, while adding another object that may be struck by vehicles. Most existing low volume road (LVR) bridges in the state of Iowa are currently indicated to not possess bridge rail meeting “current acceptable standards”. The primary objective of the research summarized in this report was to provide the nations bridge and approach rail state of practice and perform a state wide crash analysis on bridge rails and approach guardrails on LVR bridges in Iowa. In support of this objective, the criteria and guidelines used by other bridge owners were investigated, non-standard and innovative bridge and approach guardrails for LVR’s were investigated, and descriptive, statistical and economical analyses were performed on a state wide crash analysis. The state wide crash analysis found the overall number of crashes at/on the more than 17,000+ inventoried and non-inventoried LVR bridges in Iowa was fewer than 350 crashes over an eight year period, representing less than 0.1% of the statewide reportable crashes. In other words, LVR bridge crashes are fairly rare events. The majority of these crashes occurred on bridges with a traffic volume less than 100 vpd and width less than 24 ft. Similarly, the majority of the LVR bridges possess similar characteristics. Crash rates were highest for bridges with lower traffic volumes, narrower widths, and negative relative bridge widths (relative bridge width is defined as: bridge width minus roadway width). Crash rate did not appear to be effected by bridge length. Statistical analysis confirmed that the frequency of vehicle crashes was higher on bridges with a lower width compared to the roadway width. The frequency of crashes appeared to not be impacted by weather conditions, but crashes may be over represented at night or in dark conditions. Statistical analysis revealed that crashes that occurred on dark roadways were more likely to result in major injury or fatality. These findings potentially highlight the importance of appropriate delineation and signing. System wide, benefit-cost (B/C) analyses yielded very low B/C ratios for statewide bridge rail improvements. This finding is consistent with the aforementioned recommendation to address specific sites where safety concerns exist.

Evaluación del estándar SQL:1999 respecto a las características orientadas al objeto que soporta y su implementación a los SGBD object-relational

Memoria de TFC en el que se analiza el estándar SQL:1999 y se compara con PostgreeSQL y Oracle.

Image quality assessment in digital mammography: part II. NPWE as a validated alternative for contrast detail analysis.

Assessment of image quality for digital x-ray mammography systems used in European screening programs relies mainly on contrast-detail CDMAM phantom scoring and requires the acquisition and analysis of many images in order to reduce variability in threshold detectability. Part II of this study proposes an alternative method based on the detectability index (d') calculated for a non-prewhitened model observer with an eye filter (NPWE). The detectability index was calculated from the normalized noise power spectrum and image contrast, both measured from an image of a 5 cm poly(methyl methacrylate) phantom containing a 0.2 mm thick aluminium square, and the pre-sampling modulation transfer function. This was performed as a function of air kerma at the detector for 11 different digital mammography systems. These calculated d' values were compared against threshold gold thickness (T) results measured with the CDMAM test object and against derived theoretical relationships. A simple relationship was found between T and d', as a function of detector air kerma; a linear relationship was found between d' and contrast-to-noise ratio. The values of threshold thickness used to specify acceptable performance in the European Guidelines for 0.10 and 0.25 mm diameter discs were equivalent to threshold calculated detectability indices of 1.05 and 6.30, respectively. The NPWE method is a validated alternative to CDMAM scoring for use in the image quality specification, quality control and optimization of digital x-ray systems for screening mammography.

Culture in infancy : an account of a way the object "sculpts" early development.

The
 aim
 of
 this
 paper
 is
 to
 bring
 into
 consideration
 a
 way
 of
 studying
 culture
 in
 infancy.
 An
 emphasis 
is 
put 
on
 the
 role 
that 
the 
material 
object 
plays 
in 
early 
interactive
 processes. 
Accounted
 as
 a
 cultural
 artefact,
 the
 object
 is
 seen
 as
 a
 fundamental
 element
 within
 triadic
 mother‐object‐ infant
 interactions
 and
 is
 believed
 to
 be
 a
 driving
 force
 both
 for
 communicative
 and
 cognitive
 development.
 In
 order
 to
 reconsider
 the
 importance
 of
 the
 object
 in
 child
 development
 and
 to
 present
 an 
approach
 of 
studying
object
 construction,
accounts 
in 
literature 
on 
early 
communication
 development
 and
 the
 importance
 of
 the
 object
 are
 reviewed
 and
 discussed
 under
 the
 light
 of
 the
 cultural 
specificity 
of 
the 
material 
object.


Reversible cerebral vasoconstriction syndrome identification of prognostic factors.

OBJECT: Reversible cerebral vasoconstriction syndrome (RCVS) is described as a clinical and radiological entity characterized by thunderclap headaches, a reversible segmental or multifocal vasoconstriction of cerebral arteries with or without focal neurological deficits or seizures. The purpose of this study is to determine risk factors of poor outcome in patients presented a RCVS. METHODS: A retrospective multi-center review of invasive and non-invasive neurovascular imaging between January 2006 and January 2011 has identified 10 patients with criterion of reversible segmental vasoconstriction syndrome. Demographics data, vascular risks and evolution of each of these patients were analyzed. RESULTS: Seven of the ten patients were females with a mean age of 46 years. In four patients, we did not found any causative factors. Two cases presented RCVS in post-partum period between their first and their third week after delivery. The other three cases were drug-induced RCVS, mainly vaso-active drugs. Cannabis was found as the causative factor in two patient, Sumatriptan identified in one patient while cyclosporine was the causative agent in also one patient. The mean duration of clinical follow-up was 10.2 months (range: 0-28 months). Two patients had neurological sequelae: one patient kept a dysphasia and the other had a homonymous lateral hemianopia. We could not find any significant difference of the evolution between secondary RCVS and idiopathic RCVS. The only two factors, which could be correlated to the clinical outcome were the neurological status at admission and the presence of intraparenchymal abnormalities (ischemic stroke, hematoma) in brain imaging. CONCLUSIONS: Fulminant vasoconstriction resulting in progressive symptoms or death has been reported in exceptional frequency. Physicians had to remember that such evolution could happen and predict them by identifying all factors of poor prognosis (neurological status at admission, the presence of intraparenchymal abnormalities).

Improving Searching and Browsing Capabilities of Learning Object Repositories

Learning object repositories are a basic piece of virtual learning environments used for content management. Nevertheless, learning objects have special characteristics that make traditional solutions for content management ine ective. In particular, browsing and searching for learning objects cannot be based on the typical authoritative meta-data used for describing content, such as author, title or publicationdate, among others. We propose to build a social layer on top of a learning object repository, providing nal users with additional services fordescribing, rating and curating learning objects from a teaching perspective. All these interactions among users, services and resources can be captured and further analyzed, so both browsing and searching can be personalized according to user pro le and the educational context, helping users to nd the most valuable resources for their learning process. In this paper we propose to use reputation schemes and collaborative filtering techniques for improving the user interface of a DSpace based learning object repository.

Relationships between users, resources and services in learning object repositories

In this paper we describe a proposal for defining the relationships between resources, users and services in a digital repository. Nowadays, virtual learning environments are widely used but digital repositories are not fully integrated yet into the learning process. Our final goal is to provide final users with recommendation systems and reputation schemes that help them to build a true learning community around the institutional repository, taking into account their educational context (i.e. the courses they are enrolled into) and their activity (i.e. system usage by their classmates and teachers). In order to do so, we extend the basic resource concept in a traditional digital repository by adding all the educational context and other elements from end-users' profiles, thus bridging users, resources and services, and shifting from a library-centered paradigm to a learning-centered one.

Description of a robotics-oriented relational positioning methodology

This paper presents a relational positioning methodology for flexibly and intuitively specifying offline programmed robot tasks, as well as for assisting the execution of teleoperated tasks demanding precise movements.In relational positioning, the movements of an object can be restricted totally or partially by specifying its allowed positions in terms of a set of geometric constraints. These allowed positions are found by means of a 3D sequential geometric constraint solver called PMF – Positioning Mobile with respect to Fixed. PMF exploits the fact that in a set of geometric constraints, the rotational component can often be separated from the translational one and solved independently.

The building blocks of the full body ownership illusion

Previous work has reported that it is not difficult to give people the illusion of ownership over an artificial body, providing a powerful tool for the investigation of the neural and cognitive mechanisms underlying body perception and self consciousness. We present an experimental study that uses immersive virtual reality (IVR) focused on identifying the perceptual building blocks of this illusion. We systematically manipulated visuotactile and visual sensorimotor contingencies, visual perspective, and the appearance of the virtual body in order to assess their relative role and mutual interaction. Consistent results from subjective reports and physiological measures showed that a first person perspective over a fake humanoid body is essential for eliciting a body ownership illusion. We found that the illusion of ownership can be generated when the virtual body has a realistic skin tone and spatially substitutes the real body seen from a first person perspective. In this case there is no need for an additional contribution of congruent visuotactile or sensorimotor cues. Additionally, we found that the processing of incongruent perceptual cues can be modulated by the level of the illusion: when the illusion is strong, incongruent cues are not experienced as incorrect. Participants exposed to asynchronous visuotactile stimulation can experience the ownership illusion and perceive touch as originating from an object seen to contact the virtual body. Analogously, when the level of realism of the virtual body is not high enough and/or when there is no spatial overlap between the two bodies, then the contribution of congruent multisensory and/or sensorimotor cues is required for evoking the illusion. On the basis of these results and inspired by findings from neurophysiological recordings in the monkey, we propose a model that accounts for many of the results reported in the literature.

Scene representation for object monitoring

In robotics, having a 3D representation of the environment where a robot is working can be very useful. In real-life scenarios, this environment is constantly changing for example by human interaction, external agents or by the robot itself. Thus, the representation needs to be constantly updated and extended to account for these dynamic scene changes. In this work we face the problem of representing the scene where a robot is acting. Moreover, we ought to improve this representation by reusing the information obtained in previous scenes. Our goal is to build a method to represent a scene and to update it while changes are produced. In order to achieve that, different aspects of computer vision such as space representation or feature tracking are discussed